Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 27:74:457-471.
doi: 10.1146/annurev-med-043021-014005. Epub 2022 Dec 5.

Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome

Pratik Sinha  1 , Nuala J Meyer  2 , Carolyn S Calfee  3
Affiliations
Review

Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome

Pratik Sinha et al. Annu Rev Med. .

Abstract

Heterogeneity in sepsis and acute respiratory distress syndrome (ARDS) is increasingly being recognized as one of the principal barriers to finding efficacious targeted therapies. The advent of multiple high-throughput biological data ("omics"), coupled with the widespread access to increased computational power, has led to the emergence of phenotyping in critical care. Phenotyping aims to use a multitude of data to identify homogenous subgroups within an otherwise heterogenous population. Increasingly, phenotyping schemas are being applied to sepsis and ARDS to increase understanding of these clinical conditions and identify potential therapies. Here we present a selective review of the biological phenotyping schemas applied to sepsis and ARDS. Further, we outline some of the challenges involved in translating these conceptual findings to bedside clinical decision-making tools.

Keywords: ARDS; acute respiratory distress syndrome; critical care; phenotypes; precision medicine; sepsis; subphenotypes.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Schematic of approach to phenotyping where secondary analyses of biological data collected in randomised controlled trials (RCTs) and observational cohorts can be used to identify more homogeneous subgroups. Studying immune response in these phenotypes may allow more specific therapies to be discovered-leading the way to precision-based trials.
Figure 2.
Figure 2.
A summary of the high-throughput biological data that have been used in sepsis and acute respiratory distress syndrome (ARDS) and the names of the key phenotypes that have been identified using each data type. Note only those studies that have been validated in a second dataset have been included in the figures. Ref = reference. *Represent phenotypes were differential treatment responses to interventions have been observed.
Figure 3.
Figure 3.
Overview of the challenges facing the bedside implementation of biological phenotypes identified in sepsis and acute respiratory distress syndrome. ICU = Intensive Care Unit.
See this image and copyright information in PMC

References

    1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, et al. 1994. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–24 - PubMed
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, et al. 1992. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–55 - PubMed
    1. Marshall JC. 2014. Why have clinical trials in sepsis failed? Trends Mol Med 20:195–203 - PubMed
    1. Bone RC. 1996. Why sepsis trials fail. JAMA 276:565–6 - PubMed
    1. Matthay MA, McAuley DF, Ware LB. 2017. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med 5:524–34 - PubMed

Publication types